1 Duke University Medical Center, Durham, NC.
2 Emmes Corporation, Rockville, MD.
J Clin Oncol. 2019 Feb 10;37(5):367-374. doi: 10.1200/JCO.18.00053. Epub 2018 Dec 4.
Increasing the number of hematopoietic stem and progenitor cells within an umbilical cord blood (UCB) graft shortens the time to hematopoietic recovery after UCB transplantation. In this study, we assessed the safety and efficacy of a UCB graft that was expanded ex vivo in the presence of nicotinamide and transplanted after myeloablative conditioning as a stand-alone hematopoietic stem-cell graft.
Thirty-six patients with hematologic malignancies underwent transplantation at 11 sites.
The cumulative incidence of neutrophil engraftment at day 42 was 94%. Two patients experienced secondary graft failure attributable to viral infections. Hematopoietic recovery was compared with that observed in recipients of standard UCB transplantation as reported to the Center for International Blood and Marrow Transplant Research (n = 146). The median time to neutrophil recovery was 11.5 days (95% CI, 9 to 14 days) for recipients of nicotinamide-expanded UCB and 21 days (95% CI, 20 to 23 days) for the comparator ( P < .001). The median time to platelet recovery was 34 days (95% CI, 32 to 42 days) and 46 days (95% CI, 42 to 50 days) for the expanded and the comparator cohorts, respectively ( P < .001). The cumulative incidence of grade 2 to 4 acute graft-versus-host disease (GVHD) at day 100 was 44%, and grade 3 and 4 acute GVHD at day 100 was 11%. The cumulative incidence at 2 years of all chronic GVHD was 40%, and moderate/severe chronic GVHD was 10%. The 2-year cumulative incidences of nonrelapse mortality and relapse were 24% and 33%, respectively. The 2-year probabilities of overall and disease-free survival were 51% and 43%, respectively.
UCB expanded ex vivo with nicotinamide shortens median neutrophil recovery by 9.5 days (95% CI, 7 to 12 days) and median platelet recovery by 12 days (95% CI, 3 to 16.5 days). This trial establishes feasibility, safety, and efficacy of an ex vivo expanded UCB unit as a stand-alone graft.
在脐血（UCB）移植物中增加造血干细胞和祖细胞的数量可以缩短 UCB 移植后造血恢复的时间。在这项研究中，我们评估了在烟酰胺存在的情况下体外扩增的 UCB 移植物的安全性和有效性，并将其作为独立的造血干细胞移植物在清髓性预处理后进行移植。
36 例血液系统恶性肿瘤患者在 11 个中心进行了移植。
42 天中性粒细胞植入的累积发生率为 94%。两名患者因病毒感染导致继发性移植物失败。造血恢复情况与向国际血液和骨髓移植研究中心（n=146）报告的标准 UCB 移植受者的观察结果进行了比较。接受烟酰胺扩增 UCB 的患者中性粒细胞恢复的中位时间为 11.5 天（95%CI，9 至 14 天），而对照组为 21 天（95%CI，20 至 23 天）（P<0.001）。血小板恢复的中位时间分别为扩增组的 34 天（95%CI，32 至 42 天）和对照组的 46 天（95%CI，42 至 50 天）（P<0.001）。第 100 天，2 级至 4 级急性移植物抗宿主病（GVHD）的累积发生率为 44%，第 100 天 3 级和 4 级急性 GVHD 的累积发生率为 11%。2 年时所有慢性 GVHD 的累积发生率为 40%，中度/重度慢性 GVHD 的累积发生率为 10%。2 年非复发死亡率和复发率分别为 24%和 33%。2 年总生存率和无病生存率分别为 51%和 43%。
UCB 经烟酰胺体外扩增可使中性粒细胞恢复的中位数缩短 9.5 天（95%CI，7 至 12 天），血小板恢复的中位数缩短 12 天（95%CI，3 至 16.5 天）。该试验确立了体外扩增 UCB 单位作为独立移植物的可行性、安全性和有效性。
